CHARACTERIZATION OF THE HUMAN T-CELL RECEPTOR ALPHA-CHAIN REPERTOIRE AND DEMONSTRATION OF A GENETIC INFLUENCE ON V-ALPHA USAGE

Despite considerable knowledge of the determinants and profile of the T cell receptor (TCR) beta-chain repertoire, very little is known about the repertoire of the Valpha and Jalpha segments of the TCR in man or mouse. We have used the anchored polymerase chain reaction (PCR) to analyze the human TCR alpha-chain repertoire at the mRNA level in peripheral blood lymphocytes. We find marked differences in the usage of individual Valpha segments. The Valpha repertoire is determined both by differences in the use of individual Valpha gene segments at the time of gene rearrangement and by genetic influences on the selection of the expressed Valpha repertoire, presumably during thymic maturation. Analysis of the Jalpha repertoire shows non-random usage of individual Jalpha segments but no obvious relationship to chromosomal position. We also report three new Valpha segments, three new Jalpha segments and possible allelic variation in Valpha gene segments. Two unusual TCRalpha transcripts are described which add new information on the nature of TCRalpha transcript assembly.